A comprehensive review of bupleuri radix and its bioactive components： with a major focus on treating chronic liver diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleuri Radix (BR) has been recognized as an essential herbal medicine for relieving liver depression for thousands of years. Contemporary research has provided compelling evidence of its pharmacological effects, including anti-inflammatory, immunomodulatory, metabolic regulation, and anticancer properties, positioning it as a promising treatment option for various liver diseases. Hepatitis, steatohepatitis, cirrhosis, and liver cancer are among the prevalent and impactful liver diseases worldwide. However, there remains a lack of comprehensive systematic reviews that explore the prescription, bio-active components, and underlying mechanisms of BR in treating liver diseases. AIM OF THE REVIEW: To summarize the BR classical Chinese medical prescription and ingredients in treating liver diseases and their mechanisms to inform reference for further development and research. MATERIALS AND METHODS: Literature in the last three decades of BR and its classical Chinese medical prescription and ingredients were collated and summarized by searching PubMed, Wiley, Springer, Google Scholar, Web of Science, CNKI, etc. RESULTS: BR and its classical prescriptions, such as Xiao Chai Hu decoction, Da Chai Hu decoction, Si Ni San, and Chai Hu Shu Gan San, have been utilized for centuries as effective therapies for liver diseases, including hepatitis, steatohepatitis, cirrhosis, and liver cancer. BR is a rich source of active ingredients, such as saikosaponins, polysaccharides, flavonoids, sterols, organic acids, and so on. These bioactive compounds exhibit a wide range of beneficial effects, including anti-inflammatory, antioxidant, immunomodulatory, and lipid metabolism regulation. However, it is important to acknowledge that BR and its constituents can also possess hepatotoxicity, which is associated with cytochrome P450 (CYP450) enzymes and oxidative stress. Therefore, caution should be exercised when using BR in therapeutic applications to ensure the safe and appropriate utilization of its potential benefits while minimizing any potential risks. CONCLUSIONS: To sum up, BR, its compounds, and its based traditional Chinese medicine are effective in liver diseases through multiple targets, multiple pathways, and multiple effects. Advances in pharmacological and toxicological investigations of BR and its bio-active components in the future will provide further contributions to the discovery of novel therapeutics for liver diseases.

Clinical benefits of FOLFOXIRI combined with bevacizumab for advanced-stage primary signet ring cell carcinoma of the appendix: A case report.

RATIONALE: Signet-ring cell carcinoma, which is an infrequent type of colorectal cancer. Abdominal pain is the primary presenting complaint of patients with acute appendicitis. It is difficult to diagnose patients with appendiceal carcinomas accompanying with symptoms of acute appendicitis. PATIENT CONCERNS: A 33-year-old female patient was admitted to our hospital, with chief complaints of "bilateral pelvic space-occupying lesions for 1 month, aggravated abdominal distension, and she accompanied with diarrhea for 3 days." DIAGNOSIS: The patient was with primary signet ring cell carcinoma of the appendix, presented with acute appendicitis, as well as bilateral ovarian metastasis and peritoneal implantation metastasis. INTERVENTIONS: She was then treated with irinotecan, oxaliplatin, calcium folinate, 5-FU combined with bevacizumab, surgical treatment, and postoperative adjuvant treatment with oxaliplatin, capecitabine regimen to consolidate the efficacy. OUTCOMES: The patient is in good conditions, and postoperative adjuvant chemotherapy is in progress as well. CONCLUSION: The outcomes highlighted the importance of strict histopathologic assessment for appendiceal adenocarcinoma, and provided new ideas for the diagnosis and treatment of advanced-stage signet ring cell carcinoma of the appendix.

Hepatotoxic mechanism of cantharidin: insights and strategies for therapeutic intervention.

Cantharidin (CTD), a natural compound derived from Mylabris, is widely used in traditional Oriental medicine for its potent anticancer properties. However, its clinical application is restricted due to its high toxicity, particularly towards the liver. This review provides a concise understanding of the hepatotoxic mechanisms of CTD and highlights novel therapeutic strategies to mitigate its toxicity while enhancing its anticancer efficacy. We systematically explore the molecular mechanisms underlying CTD-induced hepatotoxicity, focusing on the involvement of apoptotic and autophagic processes in hepatocyte injury. We further discuss the endogenous and exogenous pathways implicated in CTD-induced liver damage and potential therapeutic targets. This review also summarizes the structural modifications of CTD derivatives and their impact on anticancer activity. Additionally, we delve into the advancements in nanoparticle-based drug delivery systems that hold promise in overcoming the limitations of CTD derivatives. By offering valuable insights into the hepatotoxic mechanisms of CTD and outlining potential avenues for future research, this review contributes to the ongoing efforts to develop safer and more effective CTD-based therapies.

Efficacy and safety of Shouhui Tongbian Capsules in the treatment of constipation: A systematic review and meta-analysis.

BACKGROUND: Constipation is a common gastrointestinal disorder, which has seriously affected the quality of people's daily life. Traditional Chinese Medicine (TCM) therapy takes syndrome differentiation and treatment as the theoretical guidance with certain advantages in treating constipation with the holistic approach. However, there are few studies on the treatment of constipation with Shouhui Tongbian Capsules (SHTB). PURPOSE: This study was aimed to evaluate the clinical effect and safety of SHTB in the treatment of constipation and provide evidence-based references for clinical application. STUDY DESIGN: A systematic review and meta-analysis of existing literature on SHTB for treating constipation. METHODS: Chinese databases (China Network Knowledge Infrastructure, Wan Fang Database and Chinese Scientific Journal Database) and English databases (PubMed, EmBase and the Cochrane Library) were thoroughly investigated through screening randomized controlled trials on SHTB for constipation from the establishment of all databases to September 26, 2022. Data extraction and quality evaluation were performed on the literature that met the inclusion criteria and a meta-analysis was performed for selected data using Review Manager 5.4, ROB 2.0 and Stata 17.0. RESULTS: A total of 14 RCTs (randomized controlled trial) including 1310 participants were included in the analysis. The results showed that the test group was superior to the control group in improving the total effective rate and curative effect, clinical symptom score, gastrointestinal peptide index and reducing adverse reactions and recurrence rate. The specific results were as follows: ① The total effective rate increased significantly (RR = 1.24, 95% CI [1.18, 1.30], Z = 8.25, p< 0.00001); ② The clinical symptom indexs, including the difficulty of defecation [SMD = -1.28, 95% CI (-1.44, -1.12), Z = 15.65, p< 0.00001], the frequency of spontaneous defecation [SMD = 1.28, 95% CI (1.01, 1.54), Z = 9.52, p< 0.00001], defecation interval [SMD = -1.47, 95% CI (-1.68, -1.26), Z = 13.79, p < 0.00001], incomplete defecation [SMD = -1.34, 95% CI (-1.57, -1.11), Z = 11.42, p < 0.00001], duration of defecation [SMD = -2.02, 95% CI (-2.39, -1.65), Z = 10.73, p < 0.00001], stool characteristics [SMD = -2.30, 95% CI (-2.60, -1.99), Z = 14.72, p< 0.00001] and TCM main syndrome scores [SMD = -1.25, 95% CI (-1.46, -1.05), Z = 11.79, p< 0.00001] increased observably; ③ The gastrointestinal peptide hormone indexs, including MTL Level [SMD = 0.43, 95% CI (0.24, 0.62), Z = 4.44, p < 0.00001] and SP Level [RR =0.57, 95% CI (0.37, 0.87), Z = 2.61, p = 0.009] were improved obviously; ④ The incidence of adverse reactions (RR = 0.57, 95% CI [0.37, 0.87], Z = 2.61, p = 0.009) and recurrence rate (RR = 0.31, 95% CI [0.18, 0.54], Z = 4.28, P <0.001) reduced significantly. Sensitivity analysis showed that there was no significant change in all outcome indicators, which suggested that the results of meta-analysis were relatively stable. Funnel plot and Egger test results showed that the literature included in the study might have publication bias. CONCLUSION: SHTB can be used to treat functional constipation, especially elderly functional constipation, constipation caused by tumor chemotherapy and disease concomitant constipation. The optimal dosage of SHTB was 0.70 g (2 capsules) each time, 3 times a day, for 28 days. Combined with basic treatment, lactose oral solution, mosaic or castor oil could improve the total effective rate, clinical symptom indicators, gastrointestinal peptide hormone indicators and reduce adverse reaction rate of patients. However, due to the limitations of the included clinical trials, high-quality clinical trials with long follow ups are needed to evaluate the effectiveness and safety of SHTB in treating different types of constipation.

Si-Ni-SAN ameliorates obesity through AKT/AMPK/HSL pathway-mediated lipolysis: Network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Ni-San (SNS) is a famous Chinese herbal formula used in China for thousands of years. It has clinical effects on a variety of lipid metabolism disorders, but the ameliorating effects of SNS on obesity and underlying mechanisms remained poorly elucidated. AIM OF THE STUDY: This study aims to explore the therapeutic effect and mechanism of SNS on obesity from multiple perspectives in vitro and in vivo. MATERIALS AND METHODS: The high-fat diet (HFD)-induced obesity mouse model was established to evaluate the effect of SNS. Then network pharmacologic methods were performed to predict underlying mechanisms, and the core pathways were verified in animal and cell studies. RESULTS: Our results demonstrated that SNS significantly reduced body weight, body fat content, white adipose tissue (WAT) expansion in obese mice, and lipid accumulation in primary mouse embryonic fibroblasts (MEFs) cells. Network pharmacologic analysis identified 66 potential therapeutic targets, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these genes revealed that the most important signaling pathway includes AMP-activated protein kinase (AMPK) signaling pathway, regulation of lipolysis in adipocytes, lipid and atherosclerosis. Western blot assay confirmed that SNS activated hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) activity and promoted lipolysis through AMPK signaling pathway. CONCLUSION: The results confirmed that SNS improves lipid accumulation through AKT/AMPK/HSL axis mediated lipolysis, which opens a new option for clinical treatment of obesity and associated complications.

Saikosaponins ameliorate hyperlipidemia in rats by enhancing hepatic lipid and cholesterol metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia is the systemic manifestation of abnormal lipid metabolism, characterized by elevated circulating levels of cholesterol and triglyceride and a high risk of cardiovascular events. Radix Bupleuri (RB) is a traditional Chinese herbal product used to treat liver diseases. Our previous study demonstrated that Saikosaponins (SSs), the most potent bioactive ingredients in RB, ameliorate hepatic steatosis. However, whether SSs have anti-hyperlipidemia effects and plausible underlying mechanisms remain elusive. AIM OF THE STUDY: To comprehensively evaluate the lipid-lowering potential of SSs against hyperlipidemia in rats. MATERIALS AND METHODS: RNA sequencing and untargeted metabolomics approaches were applied to analyze the changes in the liver transcriptome and serum lipid profile in long-term high-fat diet feeding-induced hyperlipidemia rats in response to SSs or positive drug simvastatin (SIM) intervention. RESULTS: Our data revealed that SSs significantly alleviated HFD-induced hypertriglyceridemia and hypercholesterolemia. Combined with the analysis of gene ontology enrichment analysis and gene set enrichment analysis, we found that SSs remarkably repaired the unbalanced blood lipid metabolic spectrum in a dose-dependent manner by increasing the hepatic uptake of circulating fatty acids and facilitating mitochondrial respiration in fatty acid oxidation, comparable to SIM group. In addition, SSs markedly modulated cholesterol clearance by promoting intracellular cholesterol efflux, HDL remodeling, LDL particle clearance, and bile acid synthesis. SSs also efficiently protected the liver from lipid overload-related oxidative stress and lipid peroxidation, as well as substantially exaggerated inflammatory response. CONCLUSION: Our research not only unraveled the intricate mechanisms underlying the lipid-lowering functions of SSs but also provided novel perspectives on developing an SSs-based therapeutic strategy for the treatment of hyperlipidemia. CLASSIFICATION: Metabolism.

Integrative lipidomic and transcriptomic study unravels the therapeutic effects of saikosaponins A and D on non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has become one of the most prominent causes of chronic liver diseases and malignancies. However, few therapy has been approved. Radix Bupleuri (RB) is the most frequently used herbal medicine for the treatment of liver diseases. In the current study, we aim to systemically evaluate the therapeutic effects of saikosaponin A (SSa) and saikosaponin D (SSd), the major bioactive monomers in RB, against NAFLD and to investigate the underlying mechanisms. Our results demonstrated that both SSa and SSd improved diet-induced NAFLD. Integrative lipidomic and transcriptomic analysis revealed that SSa and SSd modulated glycerolipid metabolism by regulating related genes, like Lipe and Lipg. SSd profoundly suppressed the fatty acid biosynthesis by downregulating Fasn and Acaca expression and promoted fatty acid degradation by inducing Acox1 and Cpt1a expression. Bioinformatic analysis further predicted the implication of master transcription factors, including peroxisome proliferator-activated receptor alpha (PPARα), in the protective effects of SSa and SSd. These results were further confirmed in vitro in mouse primary hepatocytes. In summary, our study uncoded the complicated mechanisms underlying the promising anti-steatosis activities of saikosaponins (SSs), and provided critical evidence inspiring the discovery of innovative therapies based on SSa and SSd for the treatment of NAFLD and related complications.

Saikosaponin a contributed to CCIN treatment by promoting neutrophil bactericidal activity via activation CBL-dependent ERK pathway.

BACKGROUND: Despite granulocyte colony-stimulating factor (GCSF) is widely used in clinical, cancer chemotherapy induced neutropenia (CCIN) infection and infection-related mortality is high for lack of functionally mature neutrophils. Generating functional neutrophils is new therapeutic approaches to reduce CCIN-associated infection and mortality. Saikosaponin a (SSA) is one of the major bioactive components of Radix Bupleuri (RB) and exerts immunoregulatory effects. PURPOSE: The present study aims to investigate the efficacy and mechanism of SSA in CCIN therapy. METHODS: SSA was applied both in vitro and in vivo to assess the efficacy of CCIN therapy. The differentiation of neutrophils was measured by Nitroblue tetrazolium (NBT) reduction assay and Giemsa staining assay. The neutrophil differentiation related real-time transcription factors were detected by quantitative PCR (RT-qPCR) and Western Blot. Bacteria killing assay was used to assess the ability of fighting infection. Network pharmacology was employed to explore the mechanism network, and the predicted pathways were validated by Western Blot. RESULTS: We found that SSA contributed to generate functional mature neutrophils which capable of fighting infection both in vitro and in vivo. Network pharmacology prediction showed 55 pathways were predicted involved in SSA against CCIN. Further validation showed that CBL-ERK1/2 pathway was activated by SSA, which could upregulate PU.1 and CEBPß expression leading to neutrophil differentiation. CONCLUSIONS: Our findings suggest a natural regimen SSA regenerates microbicidal neutrophils to effectively reduce CCIN-associated infection via activating CBL-ERK1/2 pathway, providing a rationale for future therapeutic approaches.

Saikosaponin d contributed to cancer chemotherapy induced neutropenia therapy by promoting neutrophil differentiation via activation CBL-dependent ERK pathway.

Cancer chemotherapy induced neutropenia (CCIN) is one of the most common toxicity caused by cytotoxic anticancer agents. Despite granulocyte colony-stimulating factor (GCSF) is widely used in clinical practice, the infection and infection-related mortality rate is still high for lack of functionally mature neutrophils. Saikosaponin d (SSD) is one of the major bioactive constituents of Radix Bupleuri (RB), which exerts immune-modulatory properties. We explored the function of SSD in CCIN therapy, we found that SSD contributed to generate functional mature neutrophils which capable of fighting infection both in vitro and in vivo. Network pharmacology was employed to explore the mechanism, 61 signal pathways might play an important role in CCIN treatment. Western Blot was employed to further confirm the potential pathway involved. We found CBL-ERK1/2 pathway was activated by SSD, followed by upregulating PU.1 and CEBPß expression and leading to neutrophil differentiation. Our findings suggest a natural regimen SSD which could regenerate microbicidal neutrophils to effectively reduce CCIN-associated infection via activating CBL-ERK1/2, providing a rationale for future therapeutic approaches.

Toxicity of traditional Chinese medicine herbal and mineral products.

Traditional Chinese medicine (TCM) has been used to treat numerous kinds of diseases for more than 2000 years in eastern Asian countries. A portion of the TCM herbal and mineral products are believed to be toxic according to modern standards, and are still widely prescribed in the clinic. However, some TCM products considered to be non-toxic or low-toxic have been reported to possess significant toxicological effects on different organs in both animal and human models. In this review, we define the term "toxic" in TCM, and then we summarize the advances in pharmacology and toxicology research of Toxic Traditional Chinese Medicine (TTCM), including Chinese aconite (Fu Zi), Arsenic Trioxide, Tripterygium wilfordii Hook f. (Thunder God Vine), herbal drugs derived from plants in the Aristolochiaceae Juss. family (Ma Dou Ling), and other TCM products. Finally, the compatibility art of TCM and modern pharmaceutical approaches to manage undesired toxicity of TTCM is discussed. Promoting pharmacology and toxicology studies of TTCM and non-toxic TCM is critical for the further development and safety of TCM in clinical practice.

Four new caffeoylgluconic acid positional isomers from the fruits of Evodia rutaecarpa.

Four new compounds, 4-O-trans-caffeoylgluconic acid (1), 2-O-trans-caffeoylgluconic acid (2), 3-O-trans-caffeoylgluconic acid (3), 5-O-trans-caffeoylgluconic acid (4), together with three known ones including 6-O-trans-caffeoylgluconic acid (5), neochlorogenic acid (6), chlorogenic acid (7) were obtained from the fruits of Evodia rutaecarpa. Their structure elucidation was achieved by the methods of spectroscopic analyses, including HR-ESI-MS, NMR, and by comparison with literatures. The hepatotoxicity of compounds 1-3 was evaluated by CCK-8 method. [Formula: see text].

Long-term icariin treatment ameliorates cognitive deficits via CD4+ T cell-mediated immuno-inflammatory responses in APP/PS1 mice.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder that also involves neuroinflammation in addition to many other features. Icariin (ICA) as one of the active ingredients of Chinese herbal medicine has the immunomodulating function. This study aimed to investigate the immunotherapeutic potential of ICA on AD. Methods: APP/PS1 mice and wild type C57BL/6 mice were subjected to orally ICA administration (60 mg/kg/d) for 8 months. Then, the ethological and biochemical experiments, such as Morris water maze assay, Aß ELISA, blood T cell flow cytometry, and plasma and brain cytokines array, were conducted to evaluate the effects of ICA administration. Results: ICA significantly improved spatial learning and memory retention in APP/PS1 mice. Long-term application of ICA could also reduce hippocampus Aß deposition, modulate the differentiation of CD4+ T cells, and modulate the release of inflammatory cytokines in plasma and brain tissue. Conclusion: ICA shows the neuroprotective effects via modulating the CD4+ T lymphocyte-related immuno-inflammatory responses in APP/PS1 mice and may be a promising drug against AD progression.

[Research,evaluation,industry status and development strategy of traditional Chinese medicine functional food].

With the development of social economy,people's demand for health services is growing rapidly. As health resource with Chinese characteristics,health food containing Chinese materia medica have broad prospect and great market space for development.However,at present,there are still many problems of health food containing Chinese materia media in the research,development,evaluation and market application. In addition,due to lack of theoretical support of traditional Chinese medicine(TCM) in the research and development of health food containing Chinese materia media,blurred boundaries between health food containing Chinese materia media and other health products as well as TCM are present,lacking of TCM characteristics. In the evaluation process of health food containing Chinese materia media,the construction of functional food laws,regulations and evaluation norms is relatively lagging behind,which can't meet the needs of health food containing Chinese materia media research and development,severely restricting the development of health food containing Chinese materia media. Based on the research and evaluation of health food containing Chinese materia media,the existing problems were reviewed and the reasons for the deficiencies were analyzed in this paper. Guided by the theory of TCM,based on the constitution identification in TCM,and combined with modern scientific and technological means,a new research and development mode of functional food was put forward in this paper to distinguish health food containing Chinese materia media from TCM as well as general health products. Nevertheless,we should ensure the vitality of Chinese medicine health products with original thinking and scientific and technological connotations,and accelerate the harmonious,rapid and sustainable development of Chinese medicine health industry.

[Current evaluation situation and research strategies on enhanced immune function of health food containing Chinese materia medica].

At present,the function evaluation of health food containing Chinese materia medica is in lack of theoretical support of Chinese medicine,which can't reflect the function characteristics,dose-effect relationship and mechanism of functional food. What' s more,the evaluation technology of health food containing Chinese materia medica is relatively lagging behind and has been abolished now,which seriously restricts the development of health food containing Chinese materia medica industry. The proportion of health food containing Chinese materia medica with enhancing immune function is the highest among approved products,which is up to 30.33%. By collecting,analyzing and digging the current evaluation situation of enhancing immune function of health food containing Chinese materia medica,this paper has shown that there is no difference between health food containing Chinese materia medica evaluation and other functional food evaluation. What's more,there is a lack of characteristics of traditional Chinese medicine(TCM). The technological means including evaluation of immune active substances is under-developed and the immune cell evaluation needs to be refined and improved urgently,restricting the development of health food containing Chinese materia medica industry. Therefore,the evaluation of the enhanced immune function of health food containing Chinese materia medica should be guided by health-preserving theory in TCM,and based on the identification of TCM constitution for its claim of health function. With TCM theory and modern scientific technological means,a new evaluation model for immune function enhancement of health food containing Chinese materia medica is put forward to distinguish it from other functional food and traditional medicines. Formulation of the evaluation technology and technical specifications suitable for health food containing Chinese materia medica can fundamentally ensure the healthy,orderly,fast and sustainable development of health food containing Chinese materia medica industry.

A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins.

BACKGROUND: Radix Bupleuri (RB) has been widely used in Chinese Traditional Medicine for over 2000 years and is currently marketed in China as Chai-Hu-Shu-Gan tablets and Xiao-Yao-Wan tablets. Saikosaponins (SSs, especially SSa, SSc and SSd), as the major bioactive compounds in RB, represent anti-inflammatory, anti-tumor, anti-oxidant, anti-viral and hepatoprotective effects. PURPOSE: To summarize recent findings regarding to the extraction, detection, biosynthesis, metabolism, pharmacological/toxicological effects of SSs. METHODS: Online academic databases (including PubMed, Google Scholar, Web of Science and CNKI) were searched using search terms of "Saikosaponin", "Radix Bupleuri", "Bupleurum" and combinations to include published studies of SSs primarily from 2003 to 2018. Several critical previous studies beyond this period were also included. RESULTS: 354 papers were found and 165 papers were reviewed. SSs have drawn great attention for their anti-inflammation, anti-viral and anti-cancer effects and contradictory roles in the regulation of cell apoptosis, oxidative stress and liver fibrosis. Meanwhile, increased risks of overdose-induced acute or accumulation-related chronic hepatotoxicity of SSs and RB have also been reported. However, underlying mechanisms of SSs bioactivities, the metabolism of SSs and bioactivities of SSs metabolites are largely unknown. CONCLUSION: This comprehensive review of SSs provides novel insights and perspectives on the limitations of current studies and the importance of metabolism study and the dose-pharmacological/toxic relationship of SSs for the future discovery of SSs-based therapeutic strategies and clinical safe practice.

[Research on rat models of acute liver injury with syndrome of liver depression and spleen deficiency].

This paper aimed to establish animal models which are suitable for the activity found, efficacy evaluation of herbs resistant to acute liver injury with syndrome of liver depression and spleen deficiency and new drug research and development based on corresponding of formula and syndrome. The symptoms that are suitable for evaluating the rat models of acute liver injury with syndrome of liver depression and spleen deficiency were extracted according to the evolution rule of the etiology and pathogenesis in traditional Chinese medicine and the modern pathological mechanism. Xiaoyao pill and silibin meglumine tablets were used as drug counter evidence for models in accordence with the principle of consistence of prescription and syndrome. Rats model were fed with high-lipid and low-protein fodder of different proportion and induced by intraperitoneal injection with pig serum, intragastric administration with edible alcohol once a day for 7 days. Daily record of body weight, daily food intake and daily water intake were conducted day after day in experimental session. Symptoms were also observed and evaluated by score at the same time. The contents of ALT, AST, PA, TBIL and TBA in serum were detected and histopathological changes of liver were checked at the ending of experiment. Obvious acute liver injury occurred to all rats in model groups at 1 week following model induction. Both main symptoms and secondary symptoms were consistent with syndrome manifestation of liver depression and spleen deficiency. Compared with normal control group, the activity of ALT,AST and contents of TBIL,TBA in serum increased and the content of PA decreased. Liver tissue pathological morphology showed inflammatory cells infiltration, eosinophilic or eosinophilic adipose change in hepatocytes of rats in model groups. All the above lesions manifestation could be improved by drug counterevidence. By the disproof of medicine, rat models of acute liver injury with syndrome of liver depression and spleen deficiency could be induced by fed with high-lipid and low-protein fodder which contained 89.5% cornstarch, 10% lard and 0.5% cholesterol, intraperitoneal injected with pig serum, intragastric administrated with edible alcohol for 7 days. The rat models with a low mortality could be induced in a short time and animal status were similar to syndrome performance of patients. So the rats models are suitable for the activity found, efficacy evaluation and drug discovery of herbs resistant to acute liver injury with syndrome of liver depression and spleen deficiency, and also can be used in the research of correlation between prescription and syndrome and its mechanism.